The objectives of these studies are to determine the effects of piperonyl butoxide, a widely used pesticidal synergist, on mouse liver microsomal enzyme induction. Since piperonyl butoxide acts by inhibition of drug metabolism, we will also determine the involvement of drug metabolism in the induction process. Furthermore, we will determine the effects of piperonyl butoxide on the metabolism of several carcinogens. These effects will then be correlated with biological responses to hepatocarcinogens; e.g. DNA binding, liver cell necrosis and carcinogenesis. Our primary goal for the current year is the initiation and maintenance of carcinogenicity studies to determine the effects of PB on the oncogenicity of AAF, DMN, 3-methylcholanthrene and later in the year aflatoxins. At various times throughout these studies, the metabolic pattern of each of the carcinogens will be determined. We will also continue our studies on the effects of PB on the acute toxicities of these compounds. In this light, we are planning some preliminary studies on mitochondrial effects on PB and this as a site for possible interactive mechanisms.